A Risk Factor Analysis of Axillary Web Syndrome in Patients After Breast Cancer Surgery: A Single Center Study in Korea.

OBJECTIVE: To investigate the prevalence and risk factors of axillary web syndrome (AWS) in Korean patients. METHODS: This retrospective study included a total of 189 women who underwent breast cancer surgery and received physical therapy between September 2019 and August 2020. We analyzed AWS and the correlation between the patients' demographics, underlying disease, type of surgery and chemotherapy or radiation therapy, and lymphedema. RESULTS: The prevalence of AWS was found to be 30.6%. In the univariable analysis, age, chemotherapy, and hypertension were related to AWS. Finally, the multivariable logistic regression revealed that chemotherapy (odds ratio [OR]=2.84; 95% confidence interval [CI], 1.46-5.53) and HTN (OR=2.72; 95% CI, 1.18-6.30) were the strongest risk factors of AWS. CONCLUSION: To the best of our knowledge, this was the first study that explored the risk factors of AWS in a Korean population after breast cancer surgery. As almost one-third of patients suffer from AWS after breast cancer surgery, it is essential to closely monitor the development of AWS in patients with hypertension or undergoing chemotherapy.

Candesartan and carvedilol for primary prevention of subclinical cardiotoxicity in breast cancer patients without a cardiovascular risk treated with doxorubicin.

BACKGROUND: There is no proven primary preventive strategy for doxorubicin-induced subclinical cardiotoxicity (DISC), especially among patients without a cardiovascular (CV) risk. We investigated the primary preventive effect on DISC of the concomitant use of angiotensin receptor blockers (ARBs) or beta-blockers (BBs), especially among breast cancer patients without a CV risk. METHODS: A total of 385 patients who were scheduled for doxorubicin chemotherapy were screened. Among them, 195 patients of the study populations were included and were randomly divided into two groups [candesartan 4 mg q.d. vs. carvedilol 3.125 mg q.d.] and patients who were unwilling to take one of the medications were evaluated as controls. The primary outcomes were the incidence of early DISC (DISC developing within 6 months after chemotherapy), and late DISC (DISC developing only at least 12 months after chemotherapy). RESULT: Compared with the control group (8 out of 43 patients (18.6%)), only the candesartan group (4 out of 82 patients (4.9%)) showed a significantly lower incidence of early DISC (p = 0.022). Compared with the control group, the candesartan group demonstrated a significantly reduced decrease in left ventricular ejection fraction (LVEF) throughout the study period [-1.0% vs. -3.00 (p < 0.001) at the first follow-up, -1.10% vs. -3.40(p = 0.009) at the second follow-up]. CONCLUSIONS: Among breast cancer patients without a CV risk treated with doxorubicin-containing chemotherapy, subclinical cardiotoxicity is prevalent and concomitant administration of low-dose candesartan might be effective to prevent an early decrease in LVEF. Further large-scale, randomized controlled trials will be needed to confirm our findings.

Axillary lymph node dissection is not obligatory in breast cancer patients with biopsy-proven axillary lymph node metastasis.

PURPOSE: The ACOSOG Z0011 trial demonstrated that axillary lymph node dissection (ALND) is unnecessary in select patients with cT1-2N0 tumors undergoing breast-conserving therapy with 1-2 positive sentinel lymph nodes (SLNs). However, patients with preoperatively confirmed ALN metastasis were not included and may be subjected to unnecessary ALND. The aim of this study is to identify patients who can be considered for ALND omission when the preoperative ALN biopsy results are positive. METHODS: Breast cancer patients who underwent preoperative ALN biopsy and primary surgery were retrospectively reviewed. Among patients with positive ALN biopsy results, clinicopathological and imaging characteristics were compared according to LN disease burden (1-2 positive LNs vs. ≥ 3 positive LNs). RESULTS: A total of 542 patients were included in the analysis. Among them, 225 (41.5%) patients had a preoperative positive ALN biopsy. More than 40% of the patients (n = 99, 44.0%) with a positive biopsy had only 1-2 positive ALNs. The association between nodal burden and imaging factors was strongest when ≥ 2 suspicious LNs were identified on PET/CT images (HR 8.795, 95% CI 4.756 to 13.262). More than one imaging modality showing ≥ 2 suspicious LNs was also strongly correlated with ≥ 3 positive ALNs (HR 5.148, 95% CI 2.881 to 9.200). CONCLUSIONS: Nearly half of patients with a preoperative biopsy-proven ALN metastasis had only 1-2 positive LNs on ALND. Patients meeting ACOSOG Z0011 criteria with only one suspicious LN on PET/CT or those presenting with few abnormal ALNs on only one imaging modality appear appropriate for SLNB and consideration of ALND omission.

A N0 Predicting Model for Sentinel Lymph Node Biopsy Omission in Early Breast Cancer Upstaged From Ductal Carcinoma in Situ.

BACKGROUND: A prediction model with high sensitivity for the detection of negative axillary involvement can reduce additional axillary surgery in patients with ductal carcinoma in situ (DCIS) upstaged to invasive cancer while saving patients with pure DCIS from unnecessary axillary surgeries. Using a nationwide database, we developed and validated a scoring system for guidance in selective sentinel lymph node biopsy omission. PATIENTS AND METHODS: A total of 41,895 patients with clinically node-negative breast cancer from the Korean Breast Cancer Registry were included. The study cohort was randomly divided for the development and validation of the prediction model. Missing data were filled in using multiple imputation. Factors that were significantly associated with axillary lymph node (ALN) metastasis in > 50% of datasets were included in the final prediction model. RESULTS: The frequency of ALN metastasis in the total cohort was 24.5%. After multivariable logistic regression analysis, variables that were associated with ALN metastasis were palpability, multifocality, location, size, histologic type, grade, lymphovascular invasion, hormone receptor expression, and Ki-67 level. A scoring system was developed using these factors. The areas under the receiver operating characteristic curve for the scoring system was 0.750 in both training and validating sets. The cutoff value for performing sentinel lymph node biopsy was determined as a score of 4 to obtain prediction sensitivity higher than 95%. CONCLUSIONS: A scoring system to predict the probability of ALN metastasis was developed and validated. The application of this system in the clinic may reduce unnecessary axillary surgeries in patients with DCIS and minimize additional axillary surgery for upstaged patients with invasive cancer.

Characterization of Metabolic Syndrome Risk Factors and Health-Related Behaviors in Korean Patients With Breast Cancer by Abdominal Obesity Status.

BACKGROUND: Breast cancer is the second most prevalent malignancy among Korean women. Changes in lifestyle during and after remission of breast cancer tend to increase abdominal visceral fat, leading to increased risks of metabolic syndrome and chronic diseases. PURPOSE: This cross-sectional study examined the differences in metabolic syndrome risk factors and health-related behaviors between abdominally obese and nonabdominally obese groups of Korean patients with breast cancer. METHODS: The participants were assigned to nonabdominal obesity (waist circumference < 85 cm, n = 77) and abdominal obesity (waist circumference ≥ 85 cm, n = 59) groups, and a questionnaire was used to assess the prevalence of risk factors of metabolic syndrome and health-related behaviors in each. The chi-square test and t test were used to analyze the data. RESULTS: The average age was 54.2 years in the abdominal obesity group and 51.3 years in the nonabdominal obesity group. The average blood pressure and fasting blood glucose levels were higher in the abdominal obesity than the nonabdominal obesity group (117.3/76.3 vs. 108.9/70.4 mmHg, respectively [p = .001]; 96.9 and 90.1 mg/dl, respectively [p = .007]). High-density lipoprotein cholesterol was lower in the abdominal obesity than the nonabdominal obesity group (55.4 and 62.5 mg/dl, respectively [p = .005]), whereas triglycerides were higher in the abdominal obesity than the nonabdominal obesity group (151.6 and 111.3 mg/dl, respectively [p = .006]). The prevalence of metabolic syndrome in the abdominal obesity and nonabdominal obesity groups were 42.4% and 9.1%, respectively (p = .001). Moreover, eating habits differed between the two groups, with the frequency of vegetable consumption lower in the abdominal obesity than the nonabdominal obesity group (p = .040) and the frequencies of salty and sweet food consumption and of overeating higher in the abdominal obesity than the nonabdominal obesity group. The percentage of participants who exercised for 30 minutes three times per week was 52.5% in the abdominal obesity group and 71.4% in the nonabdominal obesity group (p = .024). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: This observational study found more metabolic syndrome risk factors in the abdominal obesity group than the nonabdominal obesity group. Consumption of sweet foods and overeating were higher and the frequencies of vegetable intake and exercise were lower in the abdominal obesity group. These findings suggest that female abdominally obese patients with breast cancer exhibit health-related behaviors that require improvement and better management. Interventional programs should be developed based on the findings of this study to reduce cancer recurrence and mortality in patients with breast cancer.

Cephalic vein approach for the implantable central venous access: A retrospective review of the single institution's experiences; Cohort Study.

Long-term venous access is usually required in patients receiving chemotherapy. We hypothesized that, out of the various central line approach techniques, the cephalic vein cut-down technique can be a safe and simple alternative in terms of surgical safety, feasibility, cost-effectiveness, and functional outcomes.We retrospectively reviewed the medical records of 569 patients who underwent implantable central venous access between January 2012 and December 2014 at our hospital.We classified our cohort according to access routes, as follows: 230 patients underwent subclavian vein access, 134 patients underwent internal jugular vein access, 25 patients underwent external jugular vein access, and 119 patients underwent cephalic vein access. The cephalic vein group had a significantly longer operation time than the subclavian group (P < .01); however, there was no difference in operation time between the internal jugular vein and cephalic vein groups (P = .59). The procedure-related complications and functional outcomes of the implanted venous port during chemotherapy were comparable between the cephalic group and other groups. Additionally, body mass index, operation time, and age did not correlate with catheter dysfunction in the multivariate logistic regression analysis (P = .53; P = .66; P = .19, respectively).We suggest that a cut-down central venous catheter insertion through the cephalic vein can be performed easily and safely with no differences in surgical and clinical outcomes compared to those of conventional percutaneous approaches. Moreover, the cephalic vein approach requires no specialized equipment, including percutaneous vascular kits, tunneling instruments, and intraoperative ultrasonography. Therefore, this technique might incur less medical expenses than conventional approaches and would be helpful for both patients and surgeons.

Primary angiosarcoma of the breast: a case report.

BACKGROUND: Primary angiosarcoma of the breast is extremely rare, accounting for less than 0.05% of all primary malignancies of the breast. Here, we report here a case of primary angiosarcoma with full description of radiology and histology, including electron microscopic findings. CASE PRESENTATION: A 39-year-old woman complained of a diffuse hard mass in her right breast. She did not have any history of radiation exposure. Ultrasonography revealed a 7 cm sized mass with an irregular anechoic cystic portion replacing the entire right breast. Modified radical mastectomy was performed. The diagnosis of intermediate grade angiosarcoma was made by microscopic examination, immunohistochemical staining, and electron microscopic examination. The patient underwent four cycles of adriamycin-ifosfamide chemotherapy and received radiation therapy. Multiple bone metastases occurred 9 months after surgery and palliative treatment was given. Follow up was lost at post-operative 22 months. CONCLUSIONS: We report a rare case of intermediate grade primary angiosarcoma with detailed radiological and histological findings. Despite postoperative chemoradiation therapy, multiple metastases suggest that intermediate grade may have a more aggressive behavior.

Early Prediction of Response to Neoadjuvant Chemotherapy Using Dynamic Contrast-Enhanced MRI and Ultrasound in Breast Cancer.

Objective: To determine the diagnostic performance of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and DCE ultrasound (DCE-US) for predicting response to neoadjuvant chemotherapy (NAC) in breast cancer patients. Materials and Methods: This Institutional Review Board-approved prospective study was performed between 2014 and 2016. Thirty-nine women with breast cancer underwent DCE-US and DCE-MRI before the NAC, follow-up DCE-US after the first cycle of NAC, and follow-up DCE-MRI after the second cycle of NAC. DCE-MRI parameters (transfer constant [Ktrans], reverse constant [kep], and leakage space [Ve]) were assessed with histograms. From DCE-US, peak-enhancement, the area under the curve, wash-in rate, wash-out rate, time to peak, and rise time (RT) were obtained. After surgery, all the imaging parameters and their changes were compared with histopathologic response using the Miller-Payne Grading (MPG) system. Data from minor and good responders were compared using Wilcoxon rank sum test, chi-square test, or Fisher's exact test. Receiver operating characteristic curve analysis was used for assessing diagnostic performance to predict good response. Results: Twelve patients (30.8%) showed a good response (MPG 4 or 5) and 27 (69.2%) showed a minor response (MPG 1-3). The mean, 25th, 50th, and 75th percentiles of Ktrans and Kep of post-NAC DCE-MRI differed between the two groups. These parameters showed fair to good diagnostic performance for the prediction of response to NAC (AUC 0.76-0.81, p ≤ 0.007). Among DCE-US parameters, the percentage change in RT showed fair prediction (AUC 0.71, p = 0.023). Conclusion: Quantitative analysis of DCE-MRI and DCE-US was helpful for early prediction of response to NAC.

Intravoxel incoherent motion diffusion-weighted MRI for predicting response to neoadjuvant chemotherapy in breast cancer.

PURPOSE: To determine the diagnostic performance of intravoxel incoherent motion (IVIM) diffusion-weighted (DW) magnetic resonance imaging (MRI) parameters in predicting response to neoadjuvant chemotherapy (NAC) in breast cancer patients. MATERIALS AND METHODS: Forty-six patients with stage II or III breast cancer underwent MRI including DW imaging with 10 b values before and after 2cycles of NAC. Apparent diffusion coefficient (ADC) and IVIM parameters (D, D*, and f) were obtained using histogram analysis derived from whole-tumor volumes. After surgery, imaging parameters were compared with histopathologic responses using the Miller-Payne grading system. RESULTS: Before NAC, Dmean, D50, and D75 were higher in good responders than in minor responders (P≤0.043). After NAC, ADCmean, ADC50, ADC75, Dmean, D25, D50, and D75 were higher in good responders (P≤0.037). Skewness of ADC and D were lower in good responders after NAC (P≤0.005). Most histogram metrics of posttreatment ADC and D had similar AUC values with reasonable accuracy for prediction of good response (AUC≥0.7, P<0.05). CONCLUSION: D and ADC are useful for the prediction of response to NAC in breast cancer patients. Additional information is obtained by application of the IVIM model in DW imaging analysis and histogram analysis using whole-tumor volume data.

Improved Model for Predicting Axillary Response to Neoadjuvant Chemotherapy in Patients with Clinically Node-Positive Breast Cancer.

PURPOSE: Pathological complete response (pCR) of axillary lymph node (LN) is frequently achieved in patients with clinically node-positive breast cancer after neoadjuvant chemotherapy (NAC). Treatment of the axilla after NAC is not well established and the value of sentinel LN biopsy following NAC remains unclear. This study investigated the predictive value of axillary response following NAC and evaluated the predictive value of a model based on axillary response. METHODS: Data prospectively collected on 201 patients with clinically node-positive breast cancer who were treated with NAC and underwent axillary LN dissection (ALND) were retrieved. A model predictive of axillary pCR was developed based on clinicopathologic variables. The overall predictive ability between models was compared by receiver operating characteristic (ROC) curve analysis. RESULTS: Of 201 patients who underwent ALND after NAC, 68 (33.8%) achieved axillary pCR. Multivariate analysis using axillary LN pCR after NAC as the dependent variable showed that higher histologic grade (p=0.031; odds ratio [OR], 2.537; 95% confidence interval [CI], 1.087-5.925) and tumor response rate ≥47.1% (p=0.001; OR, 3.212; 95% CI, 1.584-6.515) were significantly associated with an increased probability of achieving axillary pCR. The area under the ROC curve for estimating axillary pCR was significantly higher in the model that included tumor response rate than in the model that excluded this rate (0.732 vs. 0.649, p=0.022). CONCLUSION: Tumor response rate was the most significant independent predictor of axillary pCR in response to NAC. The model that included tumor response rate was a significantly better predictor of axillary pCR than the model that excluded tumor response rate.

A one-day surgical-skill training course for medical students' improved surgical skills and increased interest in surgery as a career.

BACKGROUND: Despite many high-quality programs in basic surgical-skill education, the surgical skill of junior doctors varies widely. This, together with the waning interest in surgery as a career among medical students, is a serious issue confronted by hospitals and healthcare systems worldwide. We, therefore, developed and implemented an intensive one-day surgical-skill training course for two purposes; it would improve surgical skills and increase interest in surgery among medical students. METHODS: The surgical-skill training program is named Surgical Skill Weekend (SSW) and it includes hands-on training sessions for surgical-suturing techniques and advanced surgical procedures (i.e. laparoscopic and robot-assisted surgery), hybrid simulation sessions, and an operating-room session where aforementioned sessions are all put together. By the end of the program, students' improvements in surgical-suturing skills were assessed by experts in a form of checklist, and changes in the interest in a surgical career, if there were any, were answered by the students who participated in the program. RESULTS: A total of ninety-one (91) medical students participated in the 2015 and 2016 SSW courses. Their overall satisfaction level with the course was very high (Very satisfied: 78%, Quite satisfied: 22%). All of the participant's surgical-suturing skills significantly improved (median score range: 14-20, P < 0.05) and their interest in a surgical career increased significantly (from 56% to 81%, P < 0.05) by completing the program. CONCLUSIONS: An intensive and comprehensive surgical-skill training program for medical students can not only improve surgical-suturing skills but also increase interest in surgery as a career.

Sparganosis of the Unilateral Breast: A Case Report.

Sparganosis is a parasitic infection caused by the sparganum, the plercercoid of the genus Spirometra. The preoperative diagnosis of breast sparganosis is difficult in most cases because it is a rare parasitic infection less than 2% of all cases. We report a 62-year-old woman case of breast sparganosis that were confirmed by surgical removal of worms from the right breast. The radiologic images of the patient also revealed characteristic features of breast sparganosis. The patient described the migrating palpable breast mass, which strongly suggested the possibility of breast sparganosis. The treatment of choice and confirmative diagnosis for sparganosis are complete surgical extraction of the sparganum irrespective of infected site. Inspection of the mass site with detailed medical history and radiological examinations are important for preoperative diagnosis of sparganosis patients.

Reactivation of Hepatitis C Virus and Its Clinical Outcomes in Patients Treated with Systemic Chemotherapy or Immunosuppressive Therapy.

BACKGROUND/AIMS: According to the results of several studies, the outcome of hepatitis C virus (HCV) reactivation is not as severe as the outcome of hepatitis B virus reactivation. The aim of this study was to evaluate the effect of pharmacological immunosuppression on HCV reactivation. METHODS: The medical records of patients who underwent systemic chemotherapy, corticosteroid therapy, or other immunosuppressive therapies between January 2008 and March 2015 were reviewed. Subsequently, 202 patients who were seropositive for the anti-HCV antibody were enrolled. Exclusion criteria were: unavailability of data on HCV RNA levels, a history of treatment for chronic hepatitis C, and the presence of liver diseases other than a chronic HCV infection. RESULTS: Among the 120 patients enrolled in this study, hepatitis was present in 46 patients (38%). None of the patients were diagnosed with severe hepatitis. Enhanced replication of HCV was noted in nine (27%) of the 33 patients who had data available on both basal and follow-up HCV RNA loads. Reappearance of the HCV RNA from an undetectable state did not occur after treatment. The cumulative rate of enhanced HCV replication was 23% at 1 year and 30% at 2 years. CONCLUSIONS: Although enhanced HCV replication is relatively common in HCV-infected patients treated with chemotherapy or immunosuppressive therapy, it does not lead to serious sequelae.

Identifying long-term survivors among metastatic breast cancer patients undergoing primary tumor surgery.

PURPOSE: The prognostic role of primary tumor surgery in women with metastatic breast cancer at diagnosis is contentious. A subset of patients who will benefit from aggressive local treatment is needed to be identified. Using a nationwide database, we developed and validated a predictive model to identify long-term survivors among patients who had undergone primary tumor surgery. METHODS: A total of 150,043 patients were enrolled in the Korean Breast Cancer Registry between January 1990 and December 2014. Of these, 2332 (1.6%) presented with distant metastasis at diagnosis. Using Cox proportional hazards regression, we developed and validated a model that predicts survival in patients who undergo primary tumor surgery, based on the clinicopathological features of the primary tumor. RESULTS: A total of 2232 metastatic breast cancer patients were reviewed. Of these, 1541 (69.0%) patients had undergone primary tumor surgery. The 3-year survival rate was 62.6% in this subgroup. Among these patients, advanced T-stage, high-grade tumor, lymphovascular invasion, negative estrogen receptor status, high Ki-67 expression, and abnormal CA 15-3 and alkaline phosphatase levels were associated with poor survival. A prediction model was developed based on these factors, which successfully identified patients with remarkable survival (score 0-3, 3-year survival rate 87.3%). The clinical significance of the model was also validated with an independent dataset. CONCLUSIONS: We have developed a predictive model to identify long-term survivors among women who undergo primary tumor surgery. This model will provide guidance to patients and physicians when considering surgery as a treatment modality for metastatic breast cancer.

Breast Cancer Screening With Mammography Plus Ultrasonography or Magnetic Resonance Imaging in Women 50 Years or Younger at Diagnosis and Treated With Breast Conservation Therapy.

IMPORTANCE: Younger women (aged ≤50 years) who underwent breast conservation therapy may benefit from breast magnetic resonance imaging (MRI) screening as an adjunct to mammography. OBJECTIVE: To prospectively determine the cancer yield and tumor characteristics of combined mammography with MRI or ultrasonography screening in women who underwent breast conservation therapy for breast cancers and who were 50 years or younger at initial diagnosis. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, prospective, nonrandomized study was conducted from December 1, 2010, to January 31, 2016, at 6 academic institutions. Seven hundred fifty-four women who were 50 years or younger at initial diagnosis and who had undergone breast conservation therapy for breast cancer were recruited to participate in the study. Reference standard was defined as a combination of pathology and 12-month follow-up. INTERVENTIONS: Participants underwent 3 annual MRI screenings of the conserved and contralateral breasts in addition to mammography and ultrasonography, with independent readings. MAIN OUTCOMES AND MEASURES: Cancer detection rate, sensitivity, specificity, interval cancer rate, and characteristics of detected cancers. RESULTS: A total of 754 women underwent 2065 mammograms, ultrasonography, and MRI screenings. Seventeen cancers were diagnosed, and most of the detected cancers (13 of 17 [76%]) were stage 0 or stage 1. Overall cancer detection rate (8.2 vs 4.4 per 1000; P = .003) or sensitivity (100% vs 53%; P = .01) of mammography with MRI was higher than that of mammography alone. After the addition of ultrasonography, the cancer detection rate was higher than that by mammography alone (6.8 vs 4.4 per 1000; P = .03). The specificity of mammography with MRI or ultrasonography was lower than that by mammography alone (87% or 88% vs 96%; P < .001). No interval cancer was found. CONCLUSIONS AND RELEVANCE: After breast conservation therapy in women 50 years or younger, the addition of MRI to annual mammography screening improves detection of early-stage but biologically aggressive breast cancers at acceptable specificity. Results from this study can inform patient decision making on screening methods after breast conservation therapy.

The stratification of patient risk depending on the size and ratio of metastatic lymph nodes in papillary thyroid carcinoma.

BACKGROUND: The aims of this study were to identify the clinical significances of the size of metastatic lymph node (mLN) and LN ratio (LNR) and to attempt to create a risk stratification for papillary thyroid carcinoma (PTC) patients. METHODS: We investigated the 435 PTC patients who underwent radioactive iodine (RAI) ablation treatment following thyroid surgery. The patients were classified into two groups (micrometastasis (pN1mic) ≤ 0.2 cm and macrometastasis (pN1mac) > 0.2 cm) and were stratified into the following three risk groups: group I (pN1mic, LNR ≤ 0.5); group II (pN1mic, LNR > 0.5 or pN1mac, LNR ≤ 0.5); and group III (pN1mac with LNR > 0.5). And then we investigated the association of the classified groups and variable clinicopathologic factors. RESULTS: The clinical characteristics such as large tumor size, extrathyroidal extension, higher T stage, and greater number of mLN or LNR were significantly associated with pN1mac. The mean stimulated thyroglobulin levels were increased with the patient risk groups (p = 0.02). The recurrence-free survivals were significantly different between the stratified groups (p = 0.001). CONCLUSIONS: The patient groups I, II, and III may be referred to as low-, intermediate-, and high-risk groups. Clinicians should consider the possibility of recurrence, and the decisions about the application of RAI ablation based on the size of mLN and the patient's risk groups.

Cardioprotective Effect of Dexrazoxane in Patients with HER2-Positive Breast Cancer Who Receive Anthracycline Based Adjuvant Chemotherapy Followed by Trastuzumab.

PURPOSE: We intended to determine whether dexrazoxane (DZR) is cardioprotective during administration of adjuvant anthracycline-based chemotherapy followed by a 1-year trastuzumab treatment. METHODS: The medical records of 228 patients who underwent surgical resection and received adjuvant chemotherapy with trastuzumab for human epidermal growth factor receptor type 2 (HER2)-positive breast cancer between January 2010 and December 2014 were reviewed. Approximately 25% of patients received DZR prior to each administration of doxorubicin during doxorubicin with cyclophosphamide (AC) chemotherapy. DZR was not administered during the 1-year trastuzumab maintenance period. Rates of cardiac events (reduction in left ventricular ejection fraction [LVEF] by 10% or more; reduction in absolute LVEF to <45%) and cardiac event-free duration (CFD) were examined. The trastuzumab interruption rate was also assessed. RESULTS: Twelve percent of patients experienced a cardiac event. Repeated-measures analysis of variance for ejection fraction revealed a significant main effect of time, and a significant group (DZR)×time interaction. The group treated with adjuvant chemotherapy and DZR experienced significantly lower frequencies of cardiac events than the adjuvant chemotherapy only group. In multivariate analysis, DZR administration was associated with significantly fewer cardiac events. Moreover, DZR administration was an independent good prognostic factor for CFD. Only one patient (2.3%) experienced early interruption of trastuzumab in the adjuvant chemotherapy with DZR group due to cardiac toxicity, whereas 10 patients (7.6%) experienced a trastuzumab stop event in the adjuvant chemotherapy only group. CONCLUSION: DZR is cardioprotective in HER2-positive breast cancer patients who received adjuvant chemotherapy with trastuzumab. A large cohort randomized trial is needed to determine if DZR has an effect on trastuzumab interruption and completion of 12-month trastuzumab. Because cardiac toxicity has a significant negative effect on trastuzumab maintenance and quality of life, DZR administration could be considered concomitantly with anthracycline-based adjuvant chemotherapy with trastuzumab.

Clinical usefulness of the free web-based image analysis application ImmunoRatio for assessment of Ki-67 labelling index in breast cancer.

AIMS: Ki-67 is a prognostic marker in breast cancer; however, the use of the Ki-67 labelling index (LI) in clinical practice requires a consistent and easily accessible scoring method. The present study evaluated the use of the free internet-based image analysis program ImmunoRatio to score Ki-67 LI in breast cancer in comparison with manual counting. METHODS: Ki-67 immunohistochemical detection was performed in 577 breast cancer cases, and the Ki-67 LI was determined by ImmunoRatio and manual counting. RESULTS: The Ki-67 LI determined by ImmunoRatio correlated well with that obtained by manual counting. The concordance rate between ImmunoRatio and manual counting was excellent (κ coefficient of 0.881) at a Ki-67 LI cut-off value of 20%. Cases with high Ki-67 LI by ImmunoRatio were associated with poor overall survival, in particular in the hormone receptor positive group. CONCLUSIONS: The web-based automated image analysis program ImmunoRatio is an attractive alternative to manual counting to determine the Ki-67 LI in breast cancer.

Identification of large genomic rearrangement of BRCA1/2 in high risk patients in Korea.

BACKGROUND: While the majority of germline inactivating mutations in BRCA1/2 are small-scale mutations, large genomic rearrangements (LGRs) are also detected in a variable proportion of patients. However, routine genetic methods are incapable of detecting LGRs, and comprehensive genetic testing algorithm is necessary. METHODS: We performed multiplex ligation-dependent probe amplification assay for small-scale mutation negative patients at high-risk for LGR, based on previously published LGR risk criteria. The inclusion criteria for the high-risk subgroup were personal history of 1) early-onset breast cancer (diagnosed at ≤36 years); 2) two breast primaries; 3) breast cancer diagnosed at any age, with ≥1 close blood relatives (includes first-, second-, or third-degree) with breast and/or epithelial ovarian cancer; 4) both breast and epithelial ovarian cancer diagnosed at any age; and 5) epithelial ovarian cancer with ≥1 close blood relatives with breast and/or epithelial ovarian cancer. RESULTS: Two LGRs were identified. One was a heterozygous deletion of exon 19 and the other was a heterozygous duplication of exon 4-6. The prevalence of LGRs was 7% among Sanger-negative, high-risk patients, and accounted for 13% of all BRCA1 mutations and 2% of all patients. Moreover, LGRs reported in Korean patients, including our 2 newly identified cases, were found exclusively in families with at least one high-risk feature. CONCLUSIONS: Our result suggests that selective LGR screening for Sanger-negative, high-risk patients is necessary for Korean patients.

Dynamic Contrast-Enhanced MRI Perfusion Parameters as Imaging Biomarkers of Angiogenesis.

Hypoxia in the tumor microenvironment is the leading factor in angiogenesis. Angiogenesis can be identified by dynamic contrast-enhanced breast MRI (DCE MRI). Here we investigate the relationship between perfusion parameters on DCE MRI and angiogenic and prognostic factors in patients with invasive ductal carcinoma (IDC). Perfusion parameters (Ktrans, kep and ve) of 81 IDC were obtained using histogram analysis. Twenty-fifth, 50th and 75th percentile values were calculated and were analyzed for association with microvessel density (MVD), vascular endothelial growth factor (VEGF) and conventional prognostic factors. Correlation between MVD and ve50 was positive (r = 0.33). Ktrans50 was higher in tumors larger than 2 cm than in tumors smaller than 2 cm. In multivariate analysis, Ktrans50 was affected by tumor size and MVD with 12.8% explanation. There was significant association between Ktrans50 and tumor size and MVD. Therefore we conclude that DCE MRI perfusion parameters are potential imaging biomarkers for prediction of tumor angiogenesis and aggressiveness.